The compounds of formula (I) are useful intermediates for the synthesis of NO-releasing non steroidal anti inflammatory drugs (“NO-NSAIDs”). Examples of NO-NSAIDs are NO-acetylsalicylic acid, NO-diclofenac, NO-naproxen, NO-ketoprofen and NO-ibuprofen. Like conventional non steroidal anti inflammatory drugs, NO-NSAIDs have antipyretic and anti-inflammatory activity, but show reduced gastrointestinal toxicity and are endowed with further useful pharmacological properties. WO 98/25918 and WO 01/10814 in particular disclose the use of compounds of formula (I) in the preparation of NO-NSAIDs.
The production of mononitrated alkanediols on an industrial scale through reduction or hydrolysis of dinitrated alkanediols is poorly selective and troublesome, as the synthesis of dinitrated alkanediols involves problems during production, storage and transport similar to those encountered with nitroglycerine.
It is well known that the mononitration of alcohols (for example glycerin) can be usually carried out with concentrated nitric acid, optionally in the presence of sulfuric acid and urea to remove nitrous acid from the reaction mixture. However, this reaction is poorly selective and quickly leads to formation of dinitrated alkanediols due to the fact that the kinetics is not easy to control. Moreover by carrying out the same reaction on short chain alkanediols strong decomposition reactions are easily triggered. WO 98/25918 also discloses alkanediols mononitration with silver nitrate or fuming nitric acid as nitrating agents, in particular with concentrated nitric acid and acetic anhydride. The mononitration of alkanediols of formula (I) with the above methods is very poorly selective and troublesome on an industrial scale. In particular, dangerous decompositions easily occur, since a strong oxidizing agent (nitric acid) is contacted with extremely unstable substrates, in particular with alkanediols wherein A is a C2-C4 alkylene chain.
There is therefore the need to develop a more selective and safer industrial process for the mononitration of diol compounds which also allows to obtain compounds of formula (I) in good yields.